Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility

Mice lacking three epidermal barrier proteins-envoplakin, periplakin and involucrin-(EPI-/- mice) have a defective cornified layer, reduced epidermal γδ T cells, increased dermal CD4+ T cells and are resistant to developing skin tumours. The tumour-protective mechanism involves signalling between Rae-1 expressing keratinocytes and the Natural Killer Group 2D (NKG2D) receptor on immune cells, which also plays a role in host defences against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild type and EPI-/- skin. However, bacteria were 3-fold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance.Journal of Investigative Dermatology accepted article preview online, 30 September 2015.